The ghrelin and leptin responses to short-term starvation vs a carbohydrate-free diet in men with type 2 diabetes; a controlled, cross-over design study

Abstract

Background: We recently have reported the 24-hour glucose, insulin and glucagon responses to a 72-hour fast compared to a 72-hour macronutrient-sufficient, carbohydrate-free diet in men with type 2 diabetes. The 72-hour time period was used because it is the time required for the major metabolic adjustments to a lack of food to be instituted. As part of that study, ghrelin and leptin responses were monitored.

Methods: Twenty-four-hour total ghrelin and overnight fasting leptin concentrations were determined in males with type 2 diabetes when ingesting a standard, mixed meal diet (control), followed by a carbohydrate-free diet for 72 h or were starved for 72 h, using a crossover design.

Results: A rise in ghrelin concentration before and a decrease after meals was present when the standard diet was ingested. However, in contrast to literature reports in normal subjects, a circadian variation was not apparent. Meal related changes were absent with starvation. A carbohydrate-free diet resulted in a daylong decrease in ghrelin. It also resulted in a 19 % decrease in the overnight fasting leptin concentration. Leptin was decreased 54 % with total starvation.

Conclusion: Ingestion of a typical mixed-meal diet results in meal-related changes in ghrelin similar to those reported in normal subjects, although the circadian rhythm was not apparent. Except for the lack of meal-related changes, starvation did not change the concentration. A carbohydrate-free, high fat diet resulted in a daylong suppression of ghrelin. The leptin concentration was decreased by both the carbohydrate-free diet and starvation.

Trial registration: ClinicalTrials.gov Identifier: NCT01469104.

Keywords: 24-hour profile; Carbohydrate-free diet; Dietary carbohydrates; Dietary fats; Ghrelin; Leptin; Type 2 diabetes.

Fig. 1

Study Design. A standard diet consisting of 55 % carbohydrate, 15 % protein, and 30 % fat was ingested for dinner at home at 1800 h before admission, and during day 1 in the SDTU. On one occasion during days 2–4 subjects starved, on the other occasion they ingested a carbohydrate-free diet. Meals were ingested at 0800, 1200 and 1800 h. During two 24.5 h periods, from 0730 day 1 to 0800 day 2, and again from 0730 day 4 to 0800 day 5, blood was drawn a total of 42 times (3 baseline, every 15 min for 1 h after a mealtime, every 30 min for the 2nd and 3rd hours after a mealtime, and then every hour until the next mealtime

Fig. 2

Carbohydrate-Free Diet 24-hour Total Ghrelin Response. Twenty-four hour mean total ghrelin responses in 6 men with type 2 diabetes while ingesting a standard diet (top) and during the last 24 h of a 3-day a carbohydrate-free diet (bottom). B, L, D on the x-axis indicate the time of breakfast, lunch, and dinner. Insert: Control (standard) Diet (286 ± 765 pg^.hr/ml) and the CHO-free Diet (-3666 ± 1575 pg^.hr/ml) 24 h Ghrelin Net Areas. The differences in area responses are statistically significantly different (P = 0.04)

Fig. 3

Starvation 24-Hour Total Ghrelin and Insulin Responses. Twenty-four hour mean total ghrelin responses in 7 men with type 2 diabetes while ingesting a standard diet (top) and during the last 24 h of a 3-day fast (bottom). Insert: Control (standard) Diet (118 ± 1042 pg^.hr/ml) and Starvation (-56 ± 678 pg^.hr/ml) 24 h Ghrelin Net Areas. The differences in area responses were not statistically different (P = 0.72)